Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia
This clinical trial is studying the side effects of Erwinia asparaginase and what happens to the drug in the body in treating young patients with acute lymphoblastic leukemia who are allergic to PEG-asparaginase. Drugs used in chemotherapy, such as Erwinia asparaginase, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Adult Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacology and Toxicity of Erwinia Asparaginase (Erwinase®; Crisantaspase; IND 290) Following Allergy to PEG-Asparaginase in Treatment of Children With Acute Lymphoblastic Leukemia (ALL)|
- Trough serum asparaginase activity [ Time Frame: At 48 hours ] [ Designated as safety issue: No ]A Simon "minimax" two-stage design will be used to distinguish between a true response probability of 70% versus a true response probability of 50% with a significance level of 5%, 90% power.
- Plasma asparagine depletion [ Time Frame: On days 12 or 13 ] [ Designated as safety issue: No ]
- Presence of anti-Erwinia asparaginase antibodies in children treated with a course(s) of Erwinase® following clinical allergy to PEG-asparaginase by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: At baseline, prior to doses 4, 5, and 6 and on days 15 and 22 ] [ Designated as safety issue: No ]The rate of antibody formation will be described and compared informally to experience in Children's Cancer Group (CCG)-1962 and 1961. Serum asparaginase activity will be compared during Erwinase® courses as an indication of the neutralizing effect of antibodies on the enzyme effect.
- Frequency of asparaginase-related toxicities following Erwinase® treatment as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: At each course of Erwinase® treatment ] [ Designated as safety issue: Yes ]The incidence of these toxicities will be described. The percentage of patients that have Erwinase® therapy discontinued due to the above toxicities will also be estimated. With a sample size of 50, the incidence of the above toxicities can be estimated with a maximum standard error of 7%.
|Study Start Date:||February 2008|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy)
Patients receive 6 doses of Erwinia asparaginase IM on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.
Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: asparaginase
I. To determine if the 48-hour trough serum asparaginase activity is ≥ 0.1 IU/mL in young patients with acute lymphoblastic leukemia treated with Erwinia asparaginase after allergy to PEG-asparaginase.
II. To determine the frequency of asparaginase-related toxicity in these patients.
III. To characterize the pharmacokinetics of Erwinia asparaginase in these patients.
I. To compare serum asparaginase activity and serum asparagine concentration between patients treated with Erwinia asparaginase on this trial and historical controls treated with PEG-asparaginase on CCG-1961 and CCG-1962.
II. To determine the 72-hour serum asparaginase activity on days 8 or 11 or 13 based on the starting date of Erwinia asparaginase therapy.
III. To determine the presence of anti-Erwinia asparaginase antibodies in patients treated with a course(s) of Erwinia asparaginase following clinical allergy to PEG-asparaginase (PEG, pegaspargase).
IV. To determine if serum asparagine is adequately depleted on days 12 or 13 in a subset of these patients.
OUTLINE: This is a multicenter study.
Patients receive 6 doses of Erwinia asparaginase intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.
Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and antibody studies.
After completion of study treatment, patients are followed periodically.